The specific goal of my laboratory is to define molecules that promote adhesion of human keratinocytes to epidermal basement membrane. This fundamental issue is addressed in both clinical and basic investigative studies. In regard to the former, my laboratory studies patients with acquired autoimmune and inherited subepithelial bullous diseases. By defining and characterizing molecules targeted by autoantibodies in patients with acquired autoimmune bullous diseases, knowledge is gained about important structural proteins in skin as well as disease pathophysiology. My laboratory has a specific interest in bullous diseases in which patients have autoantibodies directed against bullous pemphigoid antigens 1 and 2, laminin 5 (also called epiligrin, kalinin, or nicein), and type VII collagen. Similarly, by identifying proteins that are defectively expressed in the skin of patients with inherited subepithelial bullous diseases, my laboratory hopes to develop an understanding about the key role that such proteins play in epidermal adhesion. My laboratory has a specific interest in various forms of junctional epidermolysis bullosa, inherited subepithelial bullous diseases characterized by defects in proteins that promote adhesion of basal keratinocytes to epidermal basement membrane. The study of patients with these inherited bullous diseases should lead to the identification of mutations in genes encoding adhesion molecules, the prenatal diagnosis of these disorders, and their treatment (as technology to introduce exogenous genes into human keratinocytes is developed). Building on findings in these clinical investigations, my laboratory isolates native and recombinant forms of keratinocyte adhesion molecules to investigate their interactions with each other as well as with proteins in extracellular matrix. The goal of these in vitro studies is to further our understanding of epidermal morphogenesis, homeostasis, and differentiation.